NM_003279.3:c.*86A>G

Variant names:

• chr20-45823262-T-C
• rs8860
• NM_003279.3:c.*86A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003279.3(TNNC2):​c.*86A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,306,528 control chromosomes in the GnomAD database, including 265,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31275 hom., cov: 31)
  • Exomes 𝑓: 0.64 (233726 hom.)
• Consequence: TNNC2 NM_003279.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 19 publications found

Genes affected

TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]

TNNC2 Gene-Disease associations (from GenCC):

• congenital myopathy 15

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003279.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	NM_003279.3	MANE Select	c.*86A>G		3_prime_UTR	Exon 6 of 6	NP_003270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	ENST00000372555.8	TSL:1 MANE Select	c.*86A>G		3_prime_UTR	Exon 6 of 6	ENSP00000361636.3
	TNNC2	ENST00000372557.1	TSL:3	c.*86A>G		3_prime_UTR	Exon 7 of 7	ENSP00000361638.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97244 AN: 151756 Hom.: 31240 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.635 AC: 733663 AN: 1154654 Hom.: 233726 Cov.: 14 AF XY: 0.632 AC XY: 360422 AN XY: 569892

African (AFR) AF: 0.682 AC: 16790 AN: 24634

American (AMR) AF: 0.660 AC: 14219 AN: 21536

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 10717 AN: 19622

East Asian (EAS) AF: 0.666 AC: 20703 AN: 31068

South Asian (SAS) AF: 0.554 AC: 34986 AN: 63122

European-Finnish (FIN) AF: 0.640 AC: 29201 AN: 45660

Middle Eastern (MID) AF: 0.607 AC: 2933 AN: 4832

European-Non Finnish (NFE) AF: 0.641 AC: 573976 AN: 895578

Other (OTH) AF: 0.620 AC: 30138 AN: 48602

GnomAD4 genome AF: 0.641 AC: 97337 AN: 151874 Hom.: 31275 Cov.: 31 AF XY: 0.637 AC XY: 47279 AN XY: 74234

African (AFR) AF: 0.682 AC: 28241 AN: 41438

American (AMR) AF: 0.621 AC: 9484 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3466

East Asian (EAS) AF: 0.612 AC: 3141 AN: 5132

South Asian (SAS) AF: 0.543 AC: 2612 AN: 4808

European-Finnish (FIN) AF: 0.641 AC: 6765 AN: 10548

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43055 AN: 67900

Other (OTH) AF: 0.633 AC: 1337 AN: 2112

Alfa AF: 0.638 Hom.: 99872

Bravo AF: 0.645

Asia WGS AF: 0.603 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.57
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8860; hg19: chr20-44451901; COSMIC: COSV65333233;